# Mechanisms of Anabolic Resistance in Older Humans

> **NIH NIH R01** · MAYO CLINIC ROCHESTER · 2024 · $673,650

## Abstract

Our preliminary data suggest that inflamed adipose tissue may contribute to blunted exercise response in
skeletal muscle of older adults. The objective of this project is to evaluate a hypothesis that inflamed adipose
secretes factors that activate inflammatory cascades in skeletal muscle, which may interfere with exercise-
responsive molecular pathways and contribute to dysfunctional muscle phenotypes with aging.
Aim 1 will determine how adipose tissue influences skeletal muscle function and anabolic response to
exercise in older adults. A combination of in vivo imaging and molecular phenotyping will be used to
characterize abdominal adipose tissue (AAT) and intermuscular adipose tissue (IMAT) in young and older
adults. Molecular response to acute exercise will be determined from protein synthesis rates, exercise-
responsive mRNAs, and activation of signaling proteins in muscle. This aim will evaluate the relationship
between adipose tissue inflammation and skeletal muscle phenotypes and function in older adults.
Aim 2 will identify the molecular pathways by which AAT and IMAT influence muscle phenotype and
exercise response in older adults. Primary muscle cultures and adipose conditioned media (AAT, IMAT) will
be generated from tissue collected in aim 1. Myotubes will be exposed to adipose explant media or serum
from inflamed or non-inflamed donors to evaluate their influence on molecular phenotype and response to
exercise mimetics in vitro. Chemical inhibition of canonical inflammatory pathways in muscle will be used to
determine their role in attenuating molecular response to exercise. Molecular profiling of conditioned media
and serum will be used to identify candidate molecules for subsequent experiments to assess their individual
influence on canonical exercise response pathways.
The contribution of the proposed research is expected to be in the form of new insights into the
paracrine/endocrine influence of adipose tissue on skeletal muscle responsiveness to exercise in older adults.
The knowledge gained in the proposed study will have a positive impact because anabolic resistance is
common in older adults and believed to contribute to sarcopenia, frailty, and loss of independence. This work
will provide insight into the link between adipose tissue dysfunction and skeletal muscle biology in aging with a
particular focus on distinct adipose tissue pools that are likely to have unique endocrine or paracrine influence
on skeletal muscle. We will also gain new knowledge of how targeting inflammatory pathways in adipose tissue
and skeletal muscle may enhance acute adaptations to exercise in older adults.

## Key facts

- **NIH application ID:** 10978966
- **Project number:** 1R01AG084733-01A1
- **Recipient organization:** MAYO CLINIC ROCHESTER
- **Principal Investigator:** IAN R LANZA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $673,650
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10978966

## Citation

> US National Institutes of Health, RePORTER application 10978966, Mechanisms of Anabolic Resistance in Older Humans (1R01AG084733-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10978966. Licensed CC0.

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